Phenolic hydroxy group

Comforth has reviewed literature reports and independently studied the special cases of reaction of 1 with salicylaldehyde and with 2-acetoxybenzaldehyde. Coumarins (10) are afforded in the condensation of 1 with salicylaldehyde or its imine, whereas when 2-acetoxybenzaldehyde is used, acetoxy oxazolone 12 is the major product. The initial aldol condensation product between the oxazolone and 2-acetoxybenzaldehyde is the 4-(a-hydroxybenzyl)oxazolone 11, in which base-catalyzed intramolecular transacetylation is envisioned. The product 9 (R = Ac) can either be acetylated on the phenolic hydroxy group, before or after loss of acetic acid, to yield the oxazolone 12, or it can rearrange, by a second intramolecular process catalyzed by base and acid, to the hydrocoumarin, which loses acetic acid to yield 10. When salicylaldehyde is the starting material, aldol intermediate 9 (R = H) can rearrange directly to a hydrocoumarin. Comforth also accessed pure 4-(2 -hydroxyphenylmethylene)-2-phenyloxazol-5(4//)-one (13) through hydrolysis of 12 with 88% sulfuric acid. 

The respective amide was prepared from 7-substituted 5-oxo-2,3-dihydro-5//-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acids via acid chlorides with different benzylamines (00M1P3). 6-Carboxamides were N-benzylated, and a side-chain phenolic hydroxy group was O-alkylated. 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l, 2,3-r/e]-1,4-benzoxazine-6-carboxylic acid was obtained from the ethyl ester by alkalic hydrolysis. 

The silylation-amination of 5,10-dihydroxy-l,4-dioxo-l,2,3,4-tetrahydroben-zo[g]phthalazine 281 for 27 h at 170 °C with excess N(2-aminoethyl)piperidine 282 and HMDS 2 proceeds with catalytic amounts of Ts0H-H20 to afford, via the activated persilylated intermediate in which the sensitive phenolic hydroxy groups are protected, the 1,4-bis-amine 283 in 67% yield. All conventional efforts with POCI3, PCI5, or SOCI2 to convert 281 into the corresponding 1,4-dichloro compound, to be followed by amination, resulted in failure [86] (Scheme 4.35). 

Kametani et al. (37-40) reported an abnormal Hofmann degradation of tetrahydroprotoberberine metho salts which resulted in secoberbines. From a synthetic point of view, however, this method appeared to be of little importance since other degradation products were formed as well. Furthermore, it was applicable only to derivatives with phenolic hydroxy groups at C-9 and/or C-l. 

C-9, and C-10, always with a phenolic hydroxy group at the 8a position. Moreover, they differ from one another by the oxidation state of the benzylic C-13 as well as by substitution and degree of saturation of the isoquinoline fragment. These alkaloids, classified as benzylisoquinoline alkaloids (2,70-74), have recently been called by Shamma et al. (75-77) pseudobenzyliso-quinolines originating from protoberberine alkaloids. In Table V a list of 8,8a-secoberbine alkaloids, sources, and spectral data are presented. 

In UV spectra of secobisbenzylisoquinoline alkaloids possessing a phenolic hydroxy group para to the aldehyde function, a marked bathochromic shift is observed upon addition of base. In IR spectra absorption of the lactam group appears at 1645-1640 cm-1, that of the aldehyde function in the range between 1720 and 1680 cm-1, and that of the ester group at 1710 cm-1. 

With these promoieties, the 3-phenolic hydroxy group of p-estradiol (the normally metabolized functional group) was blocked so that first-pass conjugative metabolism could be reduced. The relative bioavailability of estradiol was significantly improved when administered in these prodrug forms. A 17-fold increase was observed with the estradiol-3-salicylate. The P-estradiol-3-anthrani-late increased the systemic availability five-fold. 

Chromones are also Michael acceptors, and Scheme 18 shows how 3-bromochromone reacts with 1,3-diketones in basic media. The reaction is fairly general and the yields can be as high as 90%, moreover, phenolic furans are not common and the approach provides an effective way of protecting the phenolic hydroxy group during furan ring formation.100... 

Alternatively, polystyrene-based solutions were developed. Best results for immobilization were found when TADDOL derivatives (6) and (7) containing phenolic hydroxy groups were prepared in solution and anchored to Merrifield resin (Scheme 4.4) [66]. The authors managed to couple (7) to PS-DVB polymers with different loading and cross-Hnking degrees as weU as on polyethylene polymer which contained polyvinylbenzyl chloride chains (SMOP-3-resins). 

These compounds have very low bioavailability and short duration due to extremely rapid glucuronidation [24]. Substitution of the phenolic hydroxy group with a pyrrolo ring (Figure 7.20) gives a series of compounds with a suitable H-bond donor in the correct position (also the geometry matches that of the phenolic hydroxyl), but resistant to glucuronidation [23]. It is not sufficient to replace functionality with... 

The UV spectrum (7max 224, 245, 289, 330, and 340 nm) of carbazomycin B (261) resembled that of carbazomycin A (260), indicating a similar carbazole framework (231). The H-NMR spectrum was similar to that of carbazomycin A, except for the presence of a phenolic hydroxy group at 5 6.21 instead of the C-4 methoxy group at 5 4.13. The presence of a hydroxy group at C-4 was confirmed by the transformation of carbazomycin B into 4-deoxycarbazomycin B (reduction of O-tosylcarbazomycin B... 

B Phenolic hydroxy group very weak acid pKa 9.5. 

Examples where the phenolic hydroxy groups were utilized include the preparation of lignin epoxies by reaction with epichlorohydrin (2), esterifications with bis-acid chlorides (3) and cyanuric chloride (4), and polymerization with aziridines (5). 

The aliphatic hydroxy groups have been used as the polyol component of urethane resins (6). In many of these applications phenolic hydroxy groups have been alkoxylated to afford more aliphatic alcohols. 

---